The present invention relates to new anti-inflammatory and analgestic compositions.
There are known various anit-inflammatory agents, e.g. certain steroids (cortisone and its derivatives); acetyl salicylic acid (hereinafter called aspirin), butazolidin or indometacin. However, most of these known agents have unpleasant side effects, e.g. they cause ulcers.
It has thus been desirable to find compounds, which are useful anti-inflammatory agents, which are substantially as effective as the known anti-inflammatory agents but which have less unpleasant side effects.
M. Conrad and M. Guthzeit (Ber., 19(1886) and Ber., 20, 154 (1887) describe the preparation of 2,6-dimethyl-3,5-dicarboethoxy-4-pyridone, 2,6-dimethyl-3,5-dicarboethoxy-N-phenyl-4-pyridone, 2,6-dimethyl-3,5-dicarboethoxy-N-methyl-4-pyridone and 2,6-dimethyl-3,5-dicarboethoxy-N-acetyl-4-pyridone.
V. Ettel and J. Hebky, Coll. Czech.Chem.Com., 15, 639 (1950) and J. Hebky, Coll. Czech.Chem.Com., 16, 348 (1951) describe the synthesis of some of the same compounds as well as:
2,6-Dimethyl-3,5-dicarboethoxy-N-(p-hydroxyphenyl)-4-pyridone and its diacid; PA1 2,6-Dimethyl-3,5-dicarboethoxy-N-(m-hydroxyphenyl)-4-pyridone and its diacid; PA1 2,6-Dimethyl-3,5-dicarboethoxy-N-(4'-hydroxy-3',5'-dimethoxy phenyl)-4-pyridone and its diacid; PA1 2,6-dimethyl-3,5-dicarboethoxy-N-(p-acetamidophenyl)-4-pyridone and its diacid; PA1 1,4-bis-N,N'-(2',6'-dimethyl-3',5'-dicarboethoxy-4'-pyridone)-phenylene and its tetracid; PA1 2,6-dimethyl-3,5-dicarboethoxy-N-(p-Iodophenyl)-4-pyridone and its diacid; PA1 2,6-dimethyl-3,5-dicarboethoxy-N-(2',4'-Diiodophenyl)-4-pyridone and its diacid; PA1 2,6-dimethyl-3,5-dicarboxy-N-(4'-hydroxy-3',5'-diiodophenyl)-4-pyridone PA1 2,6-dimethyl-3,5-dicarboxy-N-(3'-hydroxy-2',4',6'-triiodophenyl)-4-pyridone .
Ettel & Hebky studied these compounds because of their interest in a novel X-Ray contrast agent for a similar use as the known diethanolamine salt of 3,5-diiodo-4-pyridone-N-acetic acid. They thus prepared and tested salts of the various above mentioned 2,6-dimethyl-N-(various Iodophenyl)-4-pyridone-3,5- dicarboxylic acids as X-Ray contrast agents.
We have now surprisingly found that certain esters of 2,6-dimethyl-N-substituted-4-pyridone-3,5-dicarboxylic acid have good anti-inflammatory properties substantially without having the unpleasant side effects of the known anti-inflammatory agents. Moreover, some of same pyridones have useful analgetic properties and some have beta-blocking properties. The free acids show substantially no activity while if the nitrogen carries no substituent the compounds are neurotoxic.